The mechanism of ion transport and their modifications by several neurotransmitters will be studied with electrophysiological techniques in isolated perfused segments (S1, S2, S3) of rabbit proximal tubules. Experiments are designed 1) to determine the passive properties of apical and basolateral membranes and paracellular pathway by measuring a) transepithelial resistance, b) apparent ratio of apical to basolateral membrane resistance, and c) cell membrane potentials. These data will allow us to calculate the equivalent electrical resistances and electromotive forces of the cell membranes. Ionic substitutions will be used to determine the ionic diffusional permeability of the cell membranes. 2) To study the effects of norepinephrine, dopamine, acetylocholine and other substances which modify fluid reabsorption on the passive properties of the cell membranes. 3) To determine the steady-state intracellular activities of Na, K and C1, by using ion-sensitive microelectrodes to define uphill and downhill transport process and to ascertain whether passive ion transport at a given membrane can be electrodiffusional. If these experiments are successful, intracellular ion activity measurements will be applied to the study of the mechanism of action of neurotransmitters which modify fluid transport. These experiments should provide a better understanding of proximal tubular function and of the regulation of fluid transport by the kidney as a whole.